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植物内生真菌を用いたケミカルバイオロジーによる抗トキソプラズマ薬の探索

利用植物内生真菌利用化学生物学寻找抗弓形虫药物

基本信息

批准号：
20F20402
负责人：
西川義文
金额：
$ 1.47万
依托单位：
Obihiro University of Agriculture and Veterinary Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2020
资助国家：
日本
起止时间：
2020-11-13 至 2023-03-31
项目状态：
已结题

项目摘要

The potent fungi from the screening processes will be applied to the isolation guided by anti-Toxoplasma and antimalaria activities (in vitro). These research steps are intended to confirm and trace the active agent(s) responsible for the anti-Toxoplasma and antimalaria activities. Firstly, each moldy media from scale-up fermentation (600 grams rice) will be extracted using methanol. The dried methanol extract will be suspended in distilled water and partitioned with hexane, chloroform, and ethyl acetate. Each fraction will be evaluated for anti-Toxoplasma activity and antimalaria. The active fraction(s) will be applied to various chromatography methods for further separations. Every step of column chromatography will be guided by anti-Toxoplasma and antimalarial activities, and only the active fractions will be further separated. LC-MS/MS profiling and molecular networking analyses for active fractions will be conducted to generate the compound's map, trace, and visualize the active components' cluster. The structures of isolated active compounds will be determined by spectroscopic methods, including nuclear magnetic resonance (NMR), high-resolution mass spectroscopy (HR-MS), and chemical derivatization. Anti-Toxoplasma and antimalaria effects on growth and cytotoxicity of isolated active compounds will also be evaluated in vitro. The efficacy of the most promising bioactive compounds will be evaluated using the mouse model. Furthermore, the potent fungi will be identified based on the ITS rDNA region.

从筛选过程中获得的有效真菌将应用于抗弓形虫和抗疟疾活性（体外）指导的分离。这些研究步骤旨在确认和追踪负责抗弓形虫和抗疟疾活性的活性药物。首先，将使用甲醇提取来自放大发酵（600克大米）的每种发霉培养基。将干燥的甲醇提取物悬浮于蒸馏水中，并用己烷、氯仿和乙酸乙酯分配。将评价各组分的抗弓形虫活性和抗疟疾活性。活性组分将应用于各种色谱方法进行进一步分离。柱层析的每一步都将以抗弓形虫和抗疟疾活性为指导，只有活性组分将被进一步分离。将对活性组分进行LC-MS/MS分析和分子网络分析，以生成化合物的图谱，跟踪和可视化活性组分的簇。分离的活性化合物的结构将通过光谱方法确定，包括核磁共振（NMR）、高分辨率质谱（HR-MS）和化学衍生。还将在体外评价分离的活性化合物对生长和细胞毒性的抗弓形虫和抗疟疾作用。将使用小鼠模型评估最有希望的生物活性化合物的功效。此外，将根据ITS rDNA区域鉴定有效的真菌。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evaluation of Mongolian compound library for potential antimalarial and anti-Toxoplasma agents

蒙古化合物库潜在抗疟和抗弓形虫药物的评价

DOI：
10.1016/j.parint.2021.102424
发表时间：
2021
期刊：
Parasitology International
影响因子：
1.9
作者：
Banzragchgarav Orkhon;Ariefta Nanang R.;Murata Toshihiro;Myagmarsuren Punsantsogvoo;Battsetseg Badgar;Battur Banzragch;Batkhuu Javzan;Nishikawa Yoshifumi
通讯作者：
Nishikawa Yoshifumi

National University of Mongolia/Mongolian University of Life Sciences(モンゴル)

蒙古国立大学/蒙古生命科学大学（蒙古）